No description available.

M.Sc. / Porphyrazines, having similar structures to porphyrins, exhibit interesting characteristics as well as applications. These mainly stem from the highly conjugated nature of these compounds, making them useful in fields ranging from functional dyes to molecular devices to biomedical applications. Of these a highlight must be the photodynamic treatment of cancer. The usefulness of porphyrazines in these fields is very closely linked to the structure of the macrocycles. Therefore it is necessary to find methods to customise these compounds in the hopes of improving the current applications as well as broaden the horizons. There exists a gap in porphyrazine synthesis in the sense that it has not been possible before to ensure the formation of cis-porphyrazines. Therefore, the main effort in this project was directed towards addressing this void. A focus of the research was to investigate introduction of a linker between two monomer dinitrile units, used during the macrocyclisation step, to force the cis geometry into the porphyrazine. Attention was also given to finding a way to functionalise the macrocycles in such a way that the functionality could be removed at a later stage to be able to differently functionalise the porphyrazines to yield other potentially interesting structures. By manipulating existing methods to prepare porphyrazines, we were able to synthesise, with a great deal of selectivity, a cis-porphyrazine from monomers that were generally viewed as trans-directors. This represented a breakthrough in porphyrazine research. It was also possible to prepare a macrocycle with removable functionality (ally! groups) on the peripheral oxygens, thereby opening up the way towards further functionalisation. Building on this success, in which two new porphyrazines (one of which was cis functionalised) had been synthesised, it was attempted to introduce the linker unit as previously described, such that cis geometry only was possible in the macrocycle. Various reaction conditions and reaction types, ranging from Mitsunobu reactions to imine formation and reduction, were utilised in various synthetic approaches to these moieties. This effort allowed the successful synthesis of a variety of linked dinitrile dimers, which were set up to undergo Linstead macrocyclisation. However due to time constraints, these compounds have not yet been subjected to macrocyclisation but represents a challenge for the future.

Increased interest in porphyrazines is due to the role they play as photosensitisers in tumour therapy. A continuing problem in photodynamic therapy is selective uptake of the photosensitiser into cancerous tissue versus healthy tissue. A potential solution would be to functionalise the photosensitiser with biological molecules to assist in its selective uptake and for enhanced water solubility. The main objective of the project was the synthesis, deprotection, metalation and characterisation of peripherally carbohydrate substituted porphyrazines. A succesful synthetic pathway for the incorporation of carbohydrate moeities into porphyrazine systems in the form of 1:3, where 1 represents the carbohydrate-substituent and 3 represents the propyl-substituted pyrrole unit, has been demonstrated by this study. To this end, a range of selectively protected monosaccharide precursors was coupled to a small variety of phthalonitriles in nucleophilic aromatic substitution reactions. The products were co-macrocyclised to form hybrid porphyrazines via Linstead macrocyclisation reactions to form the desired 1:3 cyclisation products. Similarly, two protected disaccharides were synthesised de novo, coupled with the phthalonitriles and macrocyclised into their porphyrazine derivatives. Several problems were encountered in the latter set of reactions, but various methods were devised to overcome these issues. Demetalation of the porphyrazine products mentioned above was effected with relative ease using glacial acetic acid to afford the free-base pigments, which were subsequently converted into their zinc or nickel complexes. One of the problems encountered with some of the metalated products was poor solubility in spectroscopic solvents used for their characterisation. The UV-visible spectra revealed some features related to those of free-base porphyrazines or phthalocyanines but demonstrated diagnostic unsplit Q-bands confirming the success of each metalation reaction. In the second part of this investigation, some of the porphyrazines were deprotected of their isopropylidene groups of the carbohydrates to increase their hydrophilicity. This was done by using a catalytic amount of p-TsOH acid in the presence of a nucleophilic solvent. This extraction coefficients were determined as measured between 2-octanol and PBS solution. Comparison of the partition coefficients of the carbohydrate-substituted porphyrazines and their deprotected counterparts to those of non-carbohydrate substituted pigments showed that the structural alteration offers a way to significantly increase the hydrophilicity of substituted porphyrazines. Finally, photophysical studies on the porphyrazine products were performed, and these include singlet oxygen generation, triplet lifetimes and -yields, etc. The results of this part of study showed that the products are good candidates for PDT and that the nature of the carbohydrate played an insignificant role in the activity of the pigments. Rather, the position of attachment and the presence/absence of a metal in the core cavity were found to be more important. / Prof. D.B.G. Williams

Two macrocyclic squares (one with four Pd 21 corners, the other with four Pte+ corners) were synthesized according to literature methods."2 The charge-transfer complexes which formed when each were mixed with a bis(thiol)hydroquinone were then studied by UV-VIS, NMR, and IR spectroscopy. The UV-VIS data obtained indicated a stoichiometric relationship of I mole of molecular square to 2 moles of dithiol and a very large binding constant. Further evidence for the association between each macrocyclic square and the dithiol was observed in the NMR spectrum by the shifting of the proton resonances on the bipyridine unit of the molecular square and in the IR spectra by the changes in the aromatic ring absorptions of the dithiol and the bipyridine ring absorptions of the square.A monolayer formed on gold from a dilute solution of the dithiol in ethanol and a monolayer formed from a dilute solution of a 6:1 ratio of molecular square to dithiol were each observed by infrared grazing angle spectroscopy. The spectrum of the dithiol monolayer indicated that the aromatic ring was oriented perpendicular to the gold surface. The infrared spectrum of the square/dithiol monolayer showed the presence of triflate absorptions and methyl stretches, suggesting the square was attached via a catanane formation. Furthermore, the spectral data indicated that upon formation of the catanane, the aromatic ring of the dithiol and the bipyridine rings of the square were oriented parallel to the gold surface. / Department of Chemistry

N-carboxy-α-amino acid anhydrides (NCAs) are amino acid derivatives discovered by Leuch in 1906. Ever since, they have found invaluable use in the preparation of peptide drugs and polypeptides. NCAs are generally synthesised using phosgene; however, due to the hazardous nature of this chemical, safer method of synthesis using protected amino acids in the presence of activating reagents such as P2O4, T3P, HBTU and BOP-Cl were investigated, where a protonated oxazolone intermediate is dealkylated to generate the corresponding amino acid NCA. After the successful synthesis of a variety of NCAs, starting from Boc-protected amino acids and using T3P, we attempted to work out a new method of sequential peptide synthesis using NCAs in a controlled way. The challenge involved in the use of NCAs in the synthesis of peptides is to prevent decarboxylation of the intermediate products, which lead to the generation of unwanted peptide oligomers. An elegant way to prevent the decarboxylation was studied in this work, which consists of the stabilisation of the carbamate intermediates using an appropriate receptor. We prepared several carbamate receptors and tested them in model reactions using amines and NCAs under various conditions. Despites partial success in limiting the amount of oligomerisation, we were never able to prevent it completely, and could not established conditions to prepare peptides in good purity.

No description available.

No description available.

No description available.

No description available.

No description available.